DESCRIPTION: (Applicant's Description) The long term goal of this application is for the principal investigator to develop a research career focused on the rational design, synthesis, and characterization of anticancer agents. The training acquired during the period of the award will serve as a stepping stone for the candidate to develop an independent research program in the area of anticancer drug development. The candidate will draw upon his prior research experience in the area of NMR-based macromolecular structure to accomplish his objectives. The research will be carried out under the sponsorship of Dr. Laurence H. Hurley in the Medicinal Chemistry Division of the College of Pharmacy at University of Texas Austin. Dr. Hurley's laboratory and the state of the art research facilities available within the College of Pharmacy and the University of Texas at large provide an excellent environment for the Research Career Development of the candidate. The candidate's immediate career goals are to make a contribution to anticancer drug development starting with the design, synthesis, and characterization of G-quadruplex interactive compounds as anticancer agents. Thus, the goal of the candidate's research during the period covered by the present award will be the development of anticancer agents that exert their effect by interacting with G-quadruplex DNA and/or telomerase. The specific aims of the proposed research are: (1) the determination of the effects of G-quadruplex formation on the stability of telomeric DNA-RNA hybrid duplexes, (2) the structural characterization of a carbocyanine dye complexed with G-quadruplex DNA, (3) the development of a compound that selectively cleaves G-quadruplex DNA. These aims will be accomplished using a variety of approaches involving synthetic chemistry, molecular modeling, molecular biology, UV-vis spectrophotometry and other methodologies consistent with the proposed research career plans of the candidate. The development of agents that inhibit telomere synthesis or cleave telomeric Gquadruplex DNA selectively is predicted to have a major impact on cancer treatment and the prevention of cancer cell regrowth.